Establishment of a miRNA profile in paediatric HIV-1 patients and its potential as a biomarker for effectiveness of the combined antiretroviral therapy

Irene Consuegra,Samanta Gasco,Maria Jose Mellado,María Ángeles Muñoz-Fernández,José Luis Jiménez,María Jesús Serramía

doi:10.1038/s41598-021-03020-5

Abstract

miRNAs have been extensively studied in pathological conditions, including viral infections, such as those provoked by HIV-1. Several cellular and circulating miRNAs are altered during HIV-1 infection, with either beneficial effects on host defenses or enhanced virus infectivity. Blood samples were collected in sterile EDTA tubes and plasma was separated and stored, as were PBMCs. RNA was isolated and reverse-transcribed. Finally, the miRNA gene expression profile was assessed using TaqMan Array Human microRNA Card A v2.0. A comprehensive statistical analysis was performed on the results obtained. This is the first study on miRNAs in HIV-1 paediatric patients, and a miRNA profile differentiating patients starting combination antiretroviral therapy (cART) at different times after HIV-1 diagnosis was established. Thirty-four miRNAs were observed to have different expression levels between the control group and the cART group. The data indicates the need to start cART as soon as possible after the establishment of HIV-1 infection to assure the best outcome possible. Finally, the selected 34 miRNAs may be used as biomarkers for prognosis and assessing therapy effectiveness. However, more research must be conducted to establish adequate quantitative correlations.

Highlights

MiRNAs have been extensively studied in pathological conditions, including viral infections, such as those provoked by human immunodeficiency virus type 1 (HIV-1)
MiRNAs have been extensively studied in cancer. They can shed light on processes related to infectious diseases, especially those affecting viral infections provoked by DNA and RNA viruses, such as human immunodeficiency virus type 1 (HIV-1)[8,9]
The human leukocyte antigen (HLA) alleles inherited from the mother may influence HIV infection establishment and progression in HIV-1 paediatric patients, as the virus transmitted from mother to child might have “learned” how to attack cells with those HLAs21

Summary

Introduction

MiRNAs have been extensively studied in pathological conditions, including viral infections, such as those provoked by HIV-1. Computational analysis has unveiled the potential existence of some host miRNAs that may directly affect and downregulate HIV-1 transcripts by binding to the virus itself, though the real extent of their functionality remains to be confirmed in vivo[8,12] These direct-effect miRNAs are thought to function by binding to HIV-1 transcripts coding for viral proteins, such as envelope (env), polymerase (pol), viral infectivity factor (vif), group-specific antigen (gag) and tat[13]. The tat gene induces miR-TAR, a miRNA that targets phosphatase and tensing homologue (PTEN), leading to indirect upregulation of miR-21 and miR-22 This alteration of their expression levels renders infected CD4 + T cells more resistant to apoptosis, enhancing persistence and expansion of HIV-117. It is crucial to have useful tools to predict prognosis and effectiveness of the combination therapy applied to this especially vulnerable paediatric population

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